Study of the cytotoxic effect of a peptidic inhibitor of the p53–hdm2 interaction in tumor cells

FEBS Letters

Furet, Pascal¹  Carena, Ilaria¹  Chène, Patrick¹  Fuchs, Jean¹  Garcı́a Echeverrı́a, Carlos¹ 

[1] Novartis K125 442, Oncology Department, CH-4002 Basel, Switzerland

关键词: p53;    mdm2;    Protein–protein interaction;    Apoptosis;   

DOI  :  10.1016/S0014-5793(02)03362-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Inhibitors of the p53–hdm2 interaction are attractive molecules for stimulating the p53 pathway in tumors. In this report, an inhibitor of the p53–hdm2 interaction, the AP peptide, is used to activate p53 in tumor cells expressing various levels of hdm2 protein. It induces apoptosis only in cells expressing high endogenous levels of hdm2 protein. The absence of apoptosis in tumor cells with low hdm2 levels is due not to alterations in the p53-dependent apoptotic pathway but to a different regulation of this pathway. The peptide is also less toxic for non-tumor cells than for tumor cells overexpressing the hdm2 protein.

【 授权许可】

Unknown